Lyophilization monophase solution technique for preparation of amorphous flutamide dispersions

Abstract

Flutamide (FLT) is a poorly soluble anticancer drug. Therefore, lyophilized dispersions (LDs) of FLT with polyvinylpyrrolidone (PVP) K30, polyethylene glycol (PEG) 6000, and pluronic F127 were prepared via lyophilization monophase solution technique with the aim of increasing its dissolution rate. FLT showed an A_L-type phase solubility diagrams with PVP and PEG, whereas A_N-type diagram was obtained with pluronic. The amount of residual tertiary butyl alcohol, determined by gas chromatography, was 0.015–0.021% w/w. Differential scanning calorimetry and X-ray diffractometry revealed that FLT–polymer 1:1 LDs were partially amorphous, whereas the 1:3 and 1:5 LDs were completely amorphous. After 6 months storage, polymers under study inhibited FLT recrystallization maintaining its amorphous form. The particle size of FLT–polymer LDs was between 0.81 and 2.13 μm, with a high surface area (268.43–510.82 m²/g) and porosity (354.01–676.23 e⁻³ mL/g). Also, the poor flow properties of FLT could be improved but to a limited extent. FLT dissolution was significantly enhanced with the fastest dissolution that was achieved using pluronic. After 30 min, about 66.52%, 78.23%, and 81.64% of FLT was dissolved from 1:5 FLT–PVP, PEG, and pluronic LDs, respectively, compared with only 13.45% of FLT. These data suggest that these polymers might be useful adjuncts in preparation and stabilization of amorphous immediate-release FLT LDs.

Keywords::

• Lyophilization monophase solution
• amorphous dispersions
• particle size
• surface area and porosity
• physical stability

Acknowledgement

The authors wish to thank Archimica chemical company, Italy, for kind donation of FLT used in this study.

Declaration of interest

The authors report no declarations of interest.